The present invention relates to a stereoselective synthetic method of oxazoline derivative. More particularly, it relates to a synthetic method of oxazoline derivative having the structure of formula I. ##STR2## wherein R represents phenyl, benzyl, methyl, ethyl, isopropyl, isobutyl, cyclohexyl or cyclohexylmethyl.
.beta.-amino-.alpha.-hydroxy acid has been regarded as a HIV protease inhibitor or a component of physiologically active compound. Further, taxol having the structure of formula A has been known as an efficacious anti-cancer medicine. To express the anti-cancer effect of taxol, it has been known that 3-(N-benzoylamino)-2-hydroxy-3-phenylpropionic acid has to be placed at C-13 site of the taxol. ##STR3##
The crude taxan has been isolated from the plant. However, it is hard to extract it from plant, because only a small quantity of taxan exists in the plant. Meanwhile, the semi-synthetic process from baccatin III represented by formula B has been carried out, because baccatin III can be obtained in a desirable quantity from the plant. Therefore, the stereoselective synthetic method of .beta.-amino-.alpha.-hydroxy acid which is essential chain of taxol has been regarded as very important method. ##STR4##
Such stereoselective synthetic methods of (.beta.-amino-.alpha.-hydroxy acid have been reported in following documents; Tetrahedron Letter, 35, pp 2845-2848 (1994); Tetrahedron Letter, 35, pp 9289-9292 (1994); J. Org. Chem., 59, pp 1238-1240 (1994); J. Am. Chem. Soc., 117, pp 7824-7825 (1995).
On the other hand, it has been reported that the binding reaction between hydroxy part C-13 site of baccatin III and 3-(N-benzoylamino)-2-hydroxy-3-phenylpropionic acid for preparing taxol requires severe reaction condition, and that the yield of such reaction is not quite well. To overcome such defect, the binding method using oxazoline derivative can be replaced by 3-(N-benzoylamino)-2-hydroxy-3-phenylpropionic acid [Tetrahedron Letter, 26, pp 4483-4484 (1994)].
Of course, taxol can be obtained by semi-synthetic method from baccatin III. However, the problem is how to obtain the highly purified synthetic taxol, because the purity of it affects the efficacy of taxol. Therefore, the development of synthetic method for oxazoline has important meaning due to the effect to the purity of taxol, as well as the role of intermediate of HIV protease inhibitor.